DESCRIPTION: (Principal Investigator's) This research proposal reflects our interest in the development of new reaction processes and reagents in the areas of asymmetric catalysis and acyclic stereocontrol. The objectives that we intend to pursue will focus on the development and application of chiral silane reagents, although intensive activity in methodology development is outside the scope of this program. Our short term objective(s) is to obtain a well-developed data base concerning the synthetic utility of a small number of functionalized chiral allylsilanes rather than a larger number of silane reagents with less information on their use in synthesis. A new direction to be pursued during the budget period of this proposal will focus on the improvement of existing reaction methodology concerning catalytic asymmetric carbene insertions into heteroatom-hydrogen bonds. We will also continue the development of double stereodifferentiating reactions and applications to the synthesis of antitumor antibiotics derived from terrestrial sources as well as marine sources. It is our aim to identify and develop chiral metal catalysts for the catalyzed asymmetric intermolecular carbene insertion reactions into heteroatom-hydrogen (X-H) bonds. Although an in-depth mechanistic evaluation is outside the scope of this program, it is our short term objective to develop a number of useful synthetic transformations using this methodology. As a new direction for this technology we will develop novel approaches to the synthesis of new chiral silane reagents, D or L-alpha-amino acids, alpha-hydroxy acids and alpha-thio acids. We intend to continue our efforts aimed at the completion of the asymmetric synthesis of herbimycin A. It is our continuing objective to complete the asymmetric syntheses of mycotrienin-I and trienomycin. It is our objective to complete the asymmetric synthesis of ulapualides A. We also intend to initiate the synthesis and stereochemical assignment of the related natural product kabiramide C. It is our objective to pursue the asymmetric synthesis of the phosphatase inhibitors nodularin and motuporin.